This proposal is responsive to topic #I 1, Psychoneuroimmunology. Herpesviruses commonly establish infections in humans. These infections are usually characterized by an acute phase associated with minor morbidity and mortality followed by a chronic latent phase reflecting a balance between viral replication and the host immune response. Control over herpesvirus reactivation is primarily mediated by cellular immunity which declines with advancing age. As a result, herpesvirus infections are important pathogens in the elderly and result in considerable cost to the health care system. Another factor associated with herpesvirus reactivation is stress, and there has been considerable speculation linking stress and the appearance, duration, and intensity of herpesvirus infections. The immunological decrements associated with stress are of particular concern in the elderly because they already have age-related reductions in cellular immunity. Preliminary analysis of three elderly subjects has demonstrated lytic replication of Epstein-Barr virus (EBV), a member of the herpesvirus family. Therefore, the applicant will test the hypothesis that aging will decrease EBV-specific cellular immunity and increase reactivation of latent EBV. Furthermore, stress will result in higher viral load. Importantly, little is known about the immunobiology of EBV in aging. Studies outlined in this proposal will provide preliminary data regarding age-related declines in herpesvirus-specific T-cell immunity and subsequent latent virus reactivation. These data will subsequently be used to support an R01 application to develop a mechanistic investigation on how neuroendocrine hormones modulate herpesvirus-specific immunity in the elderly.